Chin Jo-Ping, Chen Chien-Min, Lee Tsong-Hai, Chou Chii-Wen, Lu Cheng-You
Division of Neurosurgery, Tungs’ Taichung Metroharbor Hospital, Taichung 43503, Taiwan, Republic of China.
Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan, Republic of China.
Chin J Physiol. 2018 Jun 30;61(3):137-143. doi: 10.4077/CJP.2018.BAG544.
Eating of excessive raw or undercooked environmental snails produces angiostrongyliasis demyelination caused by Angiostrongylus cantonensis (A. cantonensis). The aim of this study was to investigate the association between extracellular signal-regulated kinase (Erk)1/2-nuclear factor (NF)-κB pathway and myelin basic protein (MBP) expression in RSC96 Schwann cells treated with A. cantonensis-conditioned culture medium, which was prepared by culturing the third-stage (L3) nematode larvae in DMEM for 72 h. The supernatants were collected and filtered before use. Our results showed that MBP was produced in the RSC96 cells at 16 h to 48 h post-stimulation (PS). Phosphorylated (p)-NF-κB levels were significantly increased from 8 h to 48 h PS, as were the p-Erk1/2 levels at the same time points. Additionally, expression of p-NF-κB and MBP was significantly decreased by treatment with QNZ, an NF-κB inhibitor. Treatment with PD98059, an Erk kinase inhibitor, efficiently reduced p-Erk1/2, p-NF-κB and MBP expression in the Schwann cells. These results suggest that A. cantonensis-conditioned culture medium induced suppression of the Erk1/2-NF-κB signaling pathway leading to reduced MBP production in RSC96 Schwann cells. Thus, inhibiting this signaling intermediate involved in MBP expression may be a potential method for controlling inflammatory development of A. cantonensis-induced MBP changes in preceded demyelination.
食用过多生的或未煮熟的环境蜗牛会引发由广州管圆线虫(A. cantonensis)导致的血管圆线虫病脱髓鞘。本研究的目的是探讨细胞外信号调节激酶(Erk)1/2-核因子(NF)-κB信号通路与经广州管圆线虫条件培养基处理的RSC96雪旺细胞中髓鞘碱性蛋白(MBP)表达之间的关联,该条件培养基是通过将第三期(L3)线虫幼虫在DMEM中培养72小时制备而成。收集上清液并在使用前进行过滤。我们的结果表明,在刺激后(PS)16小时至48小时,RSC96细胞中产生了MBP。磷酸化(p)-NF-κB水平在PS 8小时至48小时显著升高,同时p-Erk1/2水平在相同时间点也显著升高。此外,用NF-κB抑制剂QNZ处理可显著降低p-NF-κB和MBP的表达。用Erk激酶抑制剂PD98059处理可有效降低雪旺细胞中p-Erk1/2、p-NF-κB和MBP的表达。这些结果表明,广州管圆线虫条件培养基诱导了Erk1/2-NF-κB信号通路的抑制,导致RSC96雪旺细胞中MBP产生减少。因此,抑制参与MBP表达的这种信号中间体可能是控制广州管圆线虫诱导的脱髓鞘前期MBP变化的炎症发展的一种潜在方法。